Cellulite can result from the accumulation of degraded fatty tissue in the skin. One or several factors contributing to this disorder include poor arterial or venous circulation, hormonal disturbances and problems with lymphatic drainage. One condition underlying cellulite production is excessive fat storage in skin adipocytes. By becoming heavily laden with fat (lipids in the form of triglycerides), the adipocytes swell and become hypertrophic, sometimes to a high degree. The compression of the blood and lymph vessels by the fatty masses resulting from the hypertrophy induces poor fluid drainage and stagnation of the toxins in the skin. The edema and degeneration of connective tissue resulting from these conditions lead to the irregular stippled appearance that characterizes cellulite.
One of the goals of the skin care industry is to develop small (less than 500 MW) molecules capable of skin penetration that can stimulate the breakdown of fat deposits in cellulite and other abnormalities of the skin. It has been demonstrated that octanoic acid, a free fatty acid that is also referred to as octanoate or caprylic acid, is involved in the body's natural modulation of lipid metabolism in adipocytes (2000, Guo et al., Biochem. J. 349:463-471; 2002, Han et al., J. Nutr. 132:904-910; 2004, Lei et al., Obesity Res. 12:599-610; 2006, Guo et al., Nutr. Metab. (Lond.) 3:30; U.S. Pat. Appl. Publ. No. 2005/0019372), and therefore is a candidate drug for treating cellulite. Octanoic acid is naturally found in milk and some plant oils (e.g., coconut and palm), and is a widely used dietary supplement taken for a broad range of purposes including anti-fungal activity. Aside from its lipolytic activity, octanoic acid is also taken up by adipocytes and used along with glycerol and other fatty acid to synthesize triglycerides (FIG. 1).
Other compounds besides octanoic acid known to modulate lipid metabolism in adipocytes are primarily adapted from systemic drugs that have been developed for various heart and respiratory conditions. These include isoproterenol (a beta-adrenergic agonist), aminophylline (a phosphodiesterase inhibitor) and theophylline (a phosphodiestrase inhibitor similar in structure to caffeine). These molecules are injected as part of a mesotherapy regimen or used topically for effecting fat reduction in conditions such as cellulite deposition. To improve upon the availability of molecules such as these for application to skin care products would require producing agents that (i) are non-prescription drugs, (ii) are more natural in origin, (iii) exhibit good skin penetration qualities, and (iv) have increased lipolytic activity over the currently available molecules.